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首页> 外文期刊>Pigment cell research >The tyrosinase enhancer is activated by Sox10 and Mitf in mouse melanocytes
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The tyrosinase enhancer is activated by Sox10 and Mitf in mouse melanocytes

机译：酪氨酸酶增强剂在小鼠黑素细胞中被Sox10和Mitf激活

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摘要

The terminal differentiation of melanocytes is associated with the transcriptional activation of genes responsible for pigment production such as tyrosinase. Pigment cell-specific transcription factors, such as Mitf, as well as specific proximal and distal regulatory elements (DRE) are implicated in the tight control of tyrosinase expression during development and adulthood. Proper tyrosinase expression in melanocytes depends upon the presence of a DRE that is located at -15 kb and provides enhancer activity via a central element termed core-enhancer. In this report, we show that the transcription factors Sox10, Mitf and USF-1 are able to activate the core-enhancer in luciferase reporter assays. Comparative sequence analysis identified evolutionarily motifs resembling Sox10 binding sites that were required for full enhancer activity in melanoma cells and in tyrosinase::lacZ transgenic mice. Sox10 was able to bind the DRE in vitro and mutation of the conserved motifs abolished the enhancer transactivation mediated by Sox10. In addition, two highly conserved CAGCTG E-box motifs were identified that were also required for enhancer activity and for transactivation by Mitf. The results suggest that Sox10 directly, and Mitf, most likely indirectly, activate the tyrosinase enhancer, underlining the contribution of Sox10 to tyrosinase gene regulation in melanocytes.
机译：黑色素细胞的终末分化与负责色素生成的基因（例如酪氨酸酶）的转录激活有关。色素细胞特异性转录因子（例如Mitf）以及特定的近端和远端调节元件（DRE）与发育和成年期酪氨酸酶表达的严格控制有关。黑色素细胞中酪氨酸酶的正确表达取决于DRE的存在，该DRE位于-15 kb处，并通过称为核心增强子的中心元件提供增强子活性。在此报告中，我们显示了转录因子Sox10，Mitf和USF-1在荧光素酶报告基因检测中能够激活核心增强子。比较序列分析确定了类似于Sox10结合位点的进化基序，这是黑色素瘤细胞和酪氨酸酶:: lacZ转基因小鼠中充分增强子活性所必需的。 Sox10能够在体外结合DRE，保守基序的突变消除了Sox10介导的增强子反式激活。另外，鉴定出两个高度保守的CAGCTG E-box基序，这也是增强子活性和Mitf反式激活所必需的。结果表明，Sox10直接和Mitf最有可能间接激活酪氨酸酶增强子，从而强调了Sox10对黑素细胞酪氨酸酶基因调控的作用。

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